A Combination of Antibiotics to Decrease Neonatal Morbidity and Mortality for Previable Threatened Labor

Phase 3

Not yet recruiting

• Conditions: Previable Labour With Intact Membranes
• Interventions: Drug: Combination of antibiotics; Device: Emergency cerclage; Drug: Vaginal progesterone

• Registration Number: NCT06572761
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The purpose of this study is to determine whether a combination of antibiotics (cephalosporin 3rd generation, clarithromycin, metronidazole) are effective to prolong pregnancies complicated with previable threatened labour with intact membranes.

Detailed Description

Observational data suggest that subclinical infectious conditions can lead to spontaneous preterm labor. 10% of births are premature, but the morbidity/mortality of premature babies is concentrated mainly among newborns born before 30 weeks of gestation or weighing less than 1500 g. The relationship to infection/inflammation and premature birth is not constant throughout pregnancy, but this infectious risk increases the earlier the gestational age of spontaneous labor is (before 30 weeks). The pathogens that have the strongest associations with premature birth are Gardnerella vaginalis, Ureaplasma urealyticum and Mycoplasma hominis, but also Streptococcus B, Escherichia coli, Klebsiella spp, or Haemophilus influenzae.

Antibiotic treatment to treat an intra-amniotic infection is considered ineffective. Indeed, the last randomized trial (Oracle 2, 2001), which studied several antibiotic regimens for threatened premature delivery with intact membranes, did not find a significant reduction in neonatal morbidity/mortality after administration of co-beta-lactam, erythromycin or the combination of both. In addition, this large trial dominates the results of the latest Cochrane meta-analysis which evaluated preventive antibiotic therapy to stop premature labor with intact membranes.

Recently, it has been showed that a new combination of antibiotics (ceftriaxone, clarithromycin and metronidazole) reduced the risk of infection and intra-amniotic inflammation in preterm labor with intact membranes. This retrospective study deserves to be confirmed by a randomized study

The investigator's goal is to study whether a new combination of antibiotics in a very limited population of pregnancies complicated by the threat of late miscarriage would make it possible to prolong pregnancies in order to improve neonatal outcomes.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-23
• Study First Submitted QC: 2024-08-23
• Last Update Submitted: 2024-08-23
• Study First Posted: 2024-08-27
• Last Update Posted: 2024-08-27
• Study Start: 2024-09
• Primary Completion: 2028-05
• Study Completion: 2028-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 350

Inclusion Criteria

• Threatened previable prelabor with intact membranes between 18weeks of gestation +0/7 and 23 weeks of gestation 6/7 SA defined on endovaginal ultrasound by a short cervix ≤10 mm, and/or protrusion of the membranes on speculum examination.
• Maternal age >18 years
• Affiliated with social security
• Correct understanding of the French language
• Singleton pregnancy
• Foetus alive at time of inclusion
• Absence of regular and painful uterine contractions

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Exclusion Criteria

• Premature labor defined by regular, painful uterine contractions and a short cervix
• Protected person (patient under guardianship/curatorship/or legal protection)
• Multiple pregnancies
• Premature rupture of membranes
• Acute chorioamnionitis
• Contraindication to protocol antibiotics
• Chromosomal abnormality, congenital malformation
• Patients who received antibiotics before randomization, or requiring antibiotics for another indication (chorioamnionitis, pyelonephritis, etc.)
• Participation in another research (Specify the category: RIPH, EC, IC, etc.) or being in the exclusion period following previous research involving humans, if applicable
• Patient under AME (if no exemption from affiliation)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination of antibiotics	Combination of antibiotics	Combination of antibiotics (3rd generation of cephalosporin, clarithromycin, metronidazole) + routine care (emergency cerclage, vaginal progesterone)
Combination of antibiotics	Emergency cerclage	Combination of antibiotics (3rd generation of cephalosporin, clarithromycin, metronidazole) + routine care (emergency cerclage, vaginal progesterone)
Combination of antibiotics	Vaginal progesterone	Combination of antibiotics (3rd generation of cephalosporin, clarithromycin, metronidazole) + routine care (emergency cerclage, vaginal progesterone)
Routine care	Emergency cerclage	Routine care (emergency cerclage, vaginal progesterone)
Routine care	Vaginal progesterone	Routine care (emergency cerclage, vaginal progesterone)

Primary Outcome Measures

Name	Time	Method
A perinatal composite outcome	Up to 24 weeks	* Late miscarriage; * Perinatal mortality; * Bronchodysplasia,; * Sepsis proven by blood culture,; * Intraventricular hemorrhage ≥3,; * Periventricular leukomalacia ≥2,; * Ulcero-necrotizing enterocolitis at stage ≥2 according to the Bell classification.

Secondary Outcome Measures

Name	Time	Method
Gestationnal age at delivery	6 months	* Gestationnal age at delivery ≥ 24 weeks of gestation (wg) 0/7, 28 wg0/7, 32 wg0/7, 34 wg0/7 et 37 wg0/7; * Latency period between randomisation and delivery (≥2 days, ≥7 days, ≥14 days et ≥28 days)
Maternal Morbidty	6 months	Chorioamniotitis, postpartum endometritis , sepsis proven par positive hemocultures
Bacteriological	6 months	Acquisition of multi-resistant germs during childbirth

Trial Locations

Locations (1)

Centre Hospitalier Poissy-Saint Germain; 🇫🇷 Poissy, France